Rhogam Ultra-Filtered Plus

CLINICAL PHARMACOLOGY

Mechanism of Action

RhoGAM and MICRhoGAM act by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of action is unknown. RhoGAM, MICRhoGAM and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred.

Obstetrical Use

Use after Rh-Incompatible Transfusion

An Rh-negative individual transfused with one unit of Rh-positive red blood
cells has about an 80% likelihood of producing anti-D.4 However, Rh immunization
can occur after exposure to < 1 mL of Rh-positive red blood cells. Protection
from Rh immunization is accomplished by administering > 20 µg of RhoGAM or
MICRhoGAM per mL of Rh-positive red blood cells within 72 hours of transfusion
of incompatible red blood cells.13,22

Pharmacokinetic Properties

Pharmacokinetic studies after intramuscular injection were performed on sixteen
Rh-negative subjects receiving a single dose of (368 µg or 1840 IU) RhoGAM.10Plasma anti-D levels were monitored for thirteen weeks using a validated Automated
Quantitative Hemagglutination method with sensitivity of approximately 1 ng/mL.
The following mean pharmacokinetic parameters were obtained from data collected
over the first ten weeks of a thirteen-week study:

Parameter

Mean

SD

Units

Maximum plasma concentration obtained (Cmax)

54.0

13.0

ng/mL

Time to attain Cmax (Tmax)

4

days

Elimination half-life (T½)

30.9

13.8

days

Volume of distribution (Vd)

7.3

1.5

liters

Clearance (CL)

150.4

53.3

mL/day

Clinical Studies

Rho(D) Immune Globulin (Human) administered at 28 weeks, as well as within
72 hours of delivery, has been shown to reduce the Rh immunization rate to about
0.1-0.2%.23,24 Clinical studies demonstrated that administration
of MICRhoGAM within three hours following pregnancy termination was 100% effective
in preventing Rh immunization.25

Multiple studies have been performed that prove the safety and efficacy of RhoGAM in both the obstetrical and post transfusion settings.

Freda, Gorman and colleagues26, 27 studied the efficacy of RhoGAM
in the postpartum setting in a randomized, controlled study completed in 1967.
The control group received no immunoglobulintherapy after delivery, while the
test group received 300 µg of RhoGAM intramuscularly within 72 hours of delivery
of an Rh-positive infant. Six months after delivery, the incidence of Rh immunization
in the control group was 6.4% (32/499) versus 0.13% (1/781) in the RhoGAM group
(p < 0.001).

Pollack et al. performed two randomized, placebo-controlled studies in the
post transfusion setting that were designed to establish the dose response relationship
of RhoGAM. In the first study,15 178 (176 males, 2 females) Rh-negative
volunteers received varying volumes of Rh- positive red cells; 92 subjects then
received RhoGAM. A single dose of RhoGAM (1.1 mL @ 267 µg/mL) was shown to suppress
anti-D formation after injection of up to 15.1 mL of Rh-positive red cells.
In a companion study,4 Pollack administered 500 mL of Rh-positive whole blood
to 44 Rh-negative male volunteers. Twenty-two (22) subjects received 20 µg RhoGAM
per mL of Rh-positive red cells and 22 received no RhoGAM. None of the RhoGAM-treated
subjects developed anti-D; 18/22 control arm subjects developed anti-D (p <
0.0001).

Human clinical studies10 were subsequently performed to prove the
efficacy of MICRhoGAM and the low protein (5%) formulations. In the MICRhoGAM
study, 81 Rh-negative male volunteers received an initial injection of 2.5 mL
Rh-positive red cells, followed by a booster injection (0.1 mL) of red cells
at 26 weeks; 40 subjects received an injection of MICRhoGAM after the initial
red cell injection. None of the subjects who received MICRhoGAM developed anti-D,
both before and after the booster red cell injection. A similar study was performed
in 1985 using the low protein formulation of RhoGAM. None of the 30 Rh-negative
male volunteers who received RhoGAM after injection of 15 mL of Rh-positive
red cells developed anti-D.